反应详情

To a microwave vial was added difluorozinc (16 mg, 0.15 mmol) and Pd(tBu3P)2 (7.6 mg, 0.015 mmol). The vial was capped and purged with nitrogen for 10 minutes. DMF (1 mL) was added and the reaction mixture was allowed to stir for 10 minutes. (4-Bromo-3-methoxyphenyl)(1-methyl-1H-spiro[chromeno[4,3-c]pyrazole-4,4′-piperidine]-1′-yl)methanone (140 mg, 0.30 mmol) dissolved in DMF (0.5 mL) was added followed by trimethyl(2-methylprop-1-enoxy)silane (83 μL, 0.45 mmol). The reaction vessel was placed in an oil bath held at 80° C. for 16 hours. The reaction mixture was filtered, quenched with brine and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and evaporated to dryness. The residue was dissolved in MeOH (2 mL). NaBH4 (34 mg, 0.90 mmol) was added and the reaction mixture immediately turned from yellow to brown. The mixture was filtered and purified by HPLC (1-99%) MeOH:H2O to provide [4-(2-hydroxy-1,1-dimethyl-ethyl)-3-methoxy-phenyl]-(1-methyl-1H-spiro[chromeno[4,3-c]pyrazole-4,4′-piperidine]-1′-yl)methanone. ESI-MS m/z calc. 461.5. found 462.2 (M+1)+. Retention time: 2.73 minutes (4 min run).

1. customThe vial was capped
2. custompurged with nitrogen for 10 minutes
3. additionDMF (1 mL) was added
4. additionwas added
5. customThe reaction vessel was placed in an oil bath
6. waitheld at 80° C. for 16 hours
7. filtrationThe reaction mixture was filtered
8. customquenched with brine
9. extractionextracted with ethyl acetate
10. dry with materialThe organic layer was dried over sodium sulfate
11. filtrationfiltered
12. customevaporated to dryness
13. dissolutionThe residue was dissolved in MeOH (2 mL)
14. filtrationThe mixture was filtered
15. custompurified by HPLC (1-99%) MeOH